Lamotrigine in Pregnancy – Is Lamotrigine Safe in Pregnancy?
Lamotrigine is a synthetic phenyltriazine drug with analgesic and antiepileptic properties. It is primarily used as an anticonvulsant for the adjunctive treatment of seizures in epilepsy. Lamotrigine, in psychiatry, is used in the treatment of bipolar disorder.
Lamotrigine has multiple mechanisms of action, which give this drug its diverse anti-seizure properties as well as its novel thymoleptic and psychotropic properties.
Research shows that lamotrigine’s clinical profile is the result of distinct and overlapping mechanisms that contribute to each of its pharmacological actions. [Ketter T et al., 2003]
Central to its anti-seizure activity is its action on neuronal ion channels, particularly sodium channels and chloride channels. Proconvulsant activity is linked to Na+ influx through voltage-gated Na+ channels, which inturn leads to glutamate excitotoxicity.
Lamotrigine blocks voltage-gated Na+ channels inhibiting glutamate excitotoxicity.
Lamotrigine also enhances the release of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that attenuates neuronal electrical activity associated with paroxysms.
Lamotrigine is approved for the management of bipolar I disorder due to its stabilising effect on depressive symptoms. Lamotrigine is evidence-based in the treatment of acute depressive episodes and prophylaxis of depressive episodes as part of Bipolar I disorder. Lamotrigine also seems to have good efficacy for Bipolar II depression. Read more about mood stabilisers in the treatment of bipolar disorder.
Administration of lamotrigine is purported to have anti-glutamatergic effects as well as putative anti-kindling effects. Kindling is described as the clinical development of bipolar disorder from reactive and triggered symptoms to a more frequent, severe and spontaneously occurring form.
Although lamotrigine is commonly prescribed and has a good safety profile, a study in 2008 in the Neurology journal reported that lamotrigine exposure increased the frequency of congenital anomalies such as cleft palate in babies [Holmes L et al., 2008]. As such, the US Food and Drug Administration now includes a mandatory warning on this specific risk in patient information included with this drug.
To further test this, a new study by Dolk and colleagues aimed to determine the discrepancies in the literature by investigating the association between orofacial clefts and lamotrigine exposure during pregnancy. [Dolk H et al., 2016]